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1.
Unique species of ceramide (Cer) with very-long-chain polyunsaturated fatty acid (VLCPUFA), mainly 28–32 carbon atoms, 4–5 double bonds, in nonhydroxy and 2-hydroxy forms (n-V Cer and h-V Cer, respectively), are generated in rat spermatozoa from the corresponding sphingomyelins during the acrosomal reaction. The aim of this study was to determine the properties of these sperm-distinctive ceramides in Langmuir monolayers. Individual Cer species were isolated by HPLC and subjected to analysis of surface pressure, surface potential, and Brewster angle microscopy (BAM) as a function of molecular packing. In comparison with known species of Cer, n-V Cer and h-V Cer species showed much larger mean molecular areas and increased molecular dipole moments in liquid expanded phases, which suggest bending and partial hydration of the double bonded portion of the VLCPUFA. The presence of the 2-hydoxyl group induced a closer molecular packing in h-V Cer than in their chain-matched n-V Cer. In addition, all these Cer species showed liquid-expanded to liquid-condensed transitions at room temperature. Existence of domain segregation was confirmed by BAM. Additionally, thermodynamic analysis suggests a phase transition close to the physiological temperature for VLCPUFA-Cers if organized as bulk dispersions.  相似文献   
2.
Although it is now evident that microRNAs (miRNAs) play a critical regulatory role in many, if not all, pathological and physiological processes, remarkably they have only formally been recognized for less than fifteen years. These endogenously produced short non-coding RNAs have created a new paradigm of gene control and have utility as both novel biomarkers of cancer and as potential therapeutics. In this review we consider the role of miRNAs in lymphoid biology both under physiological (i.e. lymphopoiesis) and malignant (i.e. lymphomagenesis) conditions. In addition to the functional significance of aberrant miRNA expression in lymphomas we discuss their use as novel biomarkers, both as a in situ tumour biomarker and as a non-invasive surrogate for the tumour by testing miRNAs in the blood of patients. Finally we consider the use of these molecules as potential therapeutic agents for lymphoma (and other cancer) patients and discuss some of the hurdles yet to be overcome in order to translate this potential into clinical practice  相似文献   
3.
A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble‐based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. Proteins 2017; 85:720–730. © 2016 Wiley Periodicals, Inc.  相似文献   
4.
Truffles are prized and nutrition‐rich edible hypogeous fungi. The aim of this study was a comprehensive investigation of chemical composition of Burgundy truffle (Tuber aestivum Vittad .). We tried to answer the question: what is the impact of the environment on the truffle quality. To know the nutritional value of Burgundy truffle we compared lipids, proteins, saccharides, polyphenolics, flavonoids, total sterols, ergosterol, volatile flavour and aroma compounds content in fruit bodies of the fungus collected in three different geographical regions, i.e., Poland, Slovakia, and Italy. A comparison of the above mentioned compounds is especially interesting due to environmental and climatic differences among the studied geographical regions. Results revealed that fruit bodies of Taestivum from Poland and Slovakia possessed nearly similar content of proteins, total sterols, and saccharides. The fruiting bodies from Italy contained significantly larger amounts of most of the investigated compounds. In turn, Polish specimens had higher content of lipids and polyphenolics than Slovak and Italian ones. We have found higher similarity of volatile compounds composition between Polish and Italian specimens than those of Polish and Slovak origin.  相似文献   
5.
The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.  相似文献   
6.
During tomato (Solanum lycopersicum) fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts. It was recently reported that tomato chromoplasts can synthesize ATP through a respiratory process called chromorespiration. Here we show that chromoplast oxygen consumption is stimulated by the electron donors NADH and NADPH and is sensitive to octyl gallate (Ogal), a plastidial terminal oxidase inhibitor. The ATP synthesis rate of isolated chromoplasts was dependent on the supply of NAD(P)H and was fully inhibited by Ogal. It was also inhibited by the proton uncoupler carbonylcyanide m-chlorophenylhydrazone, suggesting the involvement of a chemiosmotic gradient. In addition, ATP synthesis was sensitive to 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, a cytochrome b6f complex inhibitor. The possible participation of this complex in chromorespiration was supported by the detection of one of its components (cytochrome f) in chromoplasts using immunoblot and immunocytochemical techniques. The observed increased expression of cytochrome c6 during ripening suggests that it could act as electron acceptor of the cytochrome b6f complex in chromorespiration. The effects of Ogal on respiration and ATP levels were also studied in tissue samples. Oxygen uptake of mature green fruit and leaf tissues was not affected by Ogal, but was inhibited increasingly in fruit pericarp throughout ripening (up to 26% in red fruit). Similarly, Ogal caused a significant decrease in ATP content of red fruit pericarp. The number of energized mitochondria, as determined by confocal microscopy, strongly decreased in fruit tissue during ripening. Therefore, the contribution of chromoplasts to total fruit respiration appears to increase in late ripening stages.Chromoplasts are plastids specialized in the production and accumulation of carotenoids, conferring color to many fruits and flowers. During tomato (Solanum lycopersicum) fruit ripening, chloroplasts differentiate into chromoplasts in a process that involves the dismantling of the photosynthetic apparatus and a massive synthesis and deposition of lycopene (Camara et al., 1995). Chromoplasts show a barely studied respiratory process, first reported for daffodil (Narcissus pseudonarcissus) chromoplasts and called chromorespiration, which consists of a membrane-bound redox pathway associated with carotenoid desaturation and results in oxygen uptake activity (Nievelstein et al., 1995). The most likely oxidase involved in this respiratory activity is the plastidial terminal oxidase (PTOX), a plastoquinol oxidase homologous to the mitochondrial alternative oxidase (AOX; Carol et al., 1999; Wu et al., 1999). According to its role in chromorespiration and in carotenoid biosynthesis, the expression of PTOX increases during the ripening process of tomato and bell pepper (Capsicum annuum) fruits (Josse et al., 2003), in parallel to chromoplast differentiation. PTOX has been characterized in vitro and it has been reported to be inhibited by pyrogallol analogs, specially by octyl gallate (Ogal; Josse et al., 2000). In vivo, PTOX has been studied mainly in chloroplasts. PTOX not only participates in carotenoid biosynthesis in chloroplasts but is also involved in chlororespiration, an electron transport chain present in thylakoids that shares plastoquinone with the photosynthetic electron transport chain (Carol and Kuntz, 2001; McDonald et al., 2011).In daffodil chromoplast homogenates (Nievelstein et al., 1995) as well as in isolated tomato fruit chromoplasts (Pateraki et al., 2013), NAD(P)H acts as an electron donor for chromorespiration, indicating the participation of NAD(P)H plastoquinone oxidoreductase activity. Considering that tomato fruit chromoplasts derive from chloroplasts, it is possible that some components of the chromoplastic redox pathway could originate from chlororespiration, such as the NAD(P)H:plastoquinone-reductase complex (NDH), which could act as the electron entrance. However, the enzymes involved in chromorespiration are not well known. It was also reported that the oxygen uptake activity of daffodil chromoplast homogenates was sensitive to the classic uncoupler 2,4-dinitrophenol (Nievelstein et al., 1995), and this observation led to the proposal that chromorespiration could be linked to membrane energization. Morstadt et al. (2002) found that liposomes containing daffodil chromoplast proteins and energized by an acid-base transition were able to produce ATP through a chemiosmotic mechanism, demonstrating that daffodil chromoplasts contain a functional H+-ATP synthase complex. We recently reported that isolated chromoplasts from tomato fruits can synthesize ATP de novo (Pateraki et al., 2013). This process is dependent on an ATP synthase complex containing an atypical γ-subunit without the regulatory dithiol domain, which may be active using lower proton gradients than those present in the chloroplast (Pateraki et al., 2013). This finding is consistent with proteomic analyses that reveal that several proteins related to electron transport and ATP production are present in chromoplasts of ripe fruits, like ATP synthase, some subunits of the NDH complex, and the cytochrome b6f complex (Barsan et al., 2012; Wang et al., 2013).Several anabolic pathways that require ATP and reducing agents are active in ripe fruit chromoplasts, such as synthesis of carotenoids, lipids (glycolipids, phospholipids, and sterols), and the shikimate pathway (Bian et al., 2011; Angaman et al., 2012). On the other hand, the ATP synthesis capacity of mitochondria in ripe fruit is low, because its membrane potential diminishes during ripening as a result of the increasing activity of the mitochondrial uncoupling protein (Almeida et al., 1999; Costa et al., 1999). This fact raised the question of whether chromorespiration could play a significant role in the production of ATP at the last stages of ripening. To our knowledge, the ATP synthesis rates of chromoplasts have not been quantified; therefore, it was uncertain whether the endogenous production could provide ATP in significant amounts to address the energy requirements of the chromoplasts. Moreover, there was no information about the quantitative contribution of chromorespiration to total fruit tissue respiration. This work aimed to deepen the study of the chromorespiratory process in isolated tomato fruit chromoplasts and to analyze the relative participation of this pathway in the overall respiration and ATP levels of fruit pericarp in vivo.  相似文献   
7.
8.
Phosphorylation of the eukaryotic translation initiation factor eIF4E is associated with malignant progression and poor cancer prognosis. Accordingly, here we have analyzed the association between eIF4E phosphorylation and cellular resistance to oxidative stress, starvation, and DNA-damaging agents in vitro. Using immortalized and cancer cell lines, retroviral expression of a phosphomimetic (S209D) form of eIF4E, but not phospho-dead (S209A) eIF4E or GFP control, significantly increased cellular resistance to stress induced by DNA-damaging agents (cisplatin), starvation (glucose+glutamine withdrawal), and oxidative stress (arsenite). De novo accumulation of eIF4E-containing cytoplasmic bodies colocalizing with the eIF4E-binding protein 4E-T was observed after expression of phosphomimetic S209D, but not S209A or wild-type eIF4E. Increased resistance to cellular stress induced by eIF4E-S209D was lost upon knockdown of endogenous 4E-T or use of an eIF4E-W73A-S209D mutant unable to bind 4E-T. Cancer cells treated with the Mnk1/2 inhibitor CGP57380 to prevent eIF4E phosphorylation and mouse embryonic fibroblasts derived from Mnk1/2 knockout mice were also more sensitive to arsenite and cisplatin treatment. Polysome analysis revealed an 80S peak 2 hours after arsenite treatment in cells overexpressing phosphomimetic eIF4E, indicating translational stalling. Nonetheless, a selective increase was observed in the synthesis of some proteins (cyclin D1, HuR, and Mcl-1). We conclude that phosphorylation of eIF4E confers resistance to various cell stressors and that a direct interaction or regulation of 4E-T by eIF4E is required. Further delineation of this process may identify novel therapeutic avenues for cancer treatment, and these results support the use of modern Mnk1/2 inhibitors in conjunction with standard therapy.  相似文献   
9.
We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10–40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.  相似文献   
10.
Greater socio-environmental instability favors the individual production of knowledge because innovations are adapted to new circumstances. Furthermore, instability stimulates the horizontal transmission of knowledge because this mechanism disseminates adapted information. This study investigates the following hypothesis: Greater socio-environmental instability favors the production of knowledge (innovation) to adapt to new situations, and socio-environmental instability stimulates the horizontal transmission of knowledge, which is a mechanism that diffuses adapted information. In addition, the present study describes “how”, “when”, “from whom” and the “stimulus/context”, in which knowledge regarding medicinal plants is gained or transferred. Data were collected through semi-structured interviews from three groups that represented different levels of socio-environmental instability. Socio-environmental instability did not favor individual knowledge production or any cultural transmission modes, including vertical to horizontal, despite increasing the frequency of horizontal pathways. Vertical transmission was the most important knowledge transmission strategy in all of the groups in which mothers were the most common models (knowledge sources). Significantly, childhood was the most important learning stage, although learning also occurred throughout life. Direct teaching using language was notable as a knowledge transmission strategy. Illness was the main stimulus that triggered local learning. Learning modes about medicinal plants were influenced by the knowledge itself, particularly the dynamic uses of therapeutic resources.  相似文献   
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